Current intrathecal chemotherapy against leptomeningeal metastasis (LM) is limited by slow diffusion through the meninges to reach the tumor deposits. Neural-axis radiotherapy is limited by radiotoxicity to the underlying neural tissues. Intrathecal injection of radionuclides may overcome both hurdles. Beta emissions from iodine-131 have long range to reach the tumors without requiring diffusion. It will deliver large radiation to tumors in the cerebral spinal fluid (CSF) and surrounding meninges while sparing the neural tissues. Gamma radiations from I-131 allow external monitoring. Others using I-131 labeled antibodies to treat LM have met partial success, limited by hematotoxicity from prolonged bone-marrow exposure to the I-131 protein fragments (half-lives of days). Specific antibodies are not available to treat most human cancers. The alternative of commonly available I-131 sodium iodide (Nal) is known for rapid renal clearance and low systemic toxicity. Exclusion of the protein moiety from the I-131 radiopharmaceutical allows rapid excretion and lower hematotoxicity. Our simulation of intralumbar injection of I-131 Nal indicated high dosimetry to ablate tumors in the CSF and low dosimetry to neural tissues. Our human studies from the first three dose levels (8 patients) of an intraventricular injection protocol (R21CA89891) have shown potential efficacy. [unreadable] Results from both the intraventricular protocol and the first 2 dose levels (4 patients) of this intralumbar protocol support our prediction of low toxicity and low radiation to neural tissues from intrathecal I-131. The intralumbar approach requires detailed investigation because of the different radiation dosimetry coverage and logistic advantages to treat LM patients before intraventricular access is established. This Phase I study aims to determine the biodistribution, radiation dosimetry, potential toxicity and efficacy of intralumbar injection of I-131 Nal to treat LM. Five to 6 groups of 3 patients with LM will be injected with escalating doses of I-131. Blood, urine samples and whole-body images will be acquired over 48-hours for biodistribution and dosimetry. The CSF cytology, MRI, thyroid, hematologic, neurologic, ophthalmologic and neuropsychologic profiles will be followed for up to 6 months to evaluate acute and sub-acute toxicity as well as efficacy. Correlation of dosages and dosimetry with toxicity and/or efficacy will be used to design future Phase II/III studies. [unreadable] [unreadable]